Reward system dysfunction is evident across neuropsychiatric conditions. Here we present data from a double-blinded pharmaco-fMRI study investigating the triggering of anhedonia and reward circuit ...activity in women.
The hormonal states of pregnancy and parturition were simulated in euthymic women with a history of postpartum depression (PPD+; n = 15) and those without such a history (PPD−; n = 15) by inducing hypogonadism, adding back estradiol and progesterone for 8 weeks (“addback”), and then withdrawing both steroids (“withdrawal”). Anhedonia was assessed using the Inventory of Depression and Anxiety Symptoms (IDAS) during each hormone phase. Those who reported a 30 % or greater increase in IDAS anhedonia, dysphoria, or ill temper during addback or withdrawal, compared with pre-treatment, were identified as hormone sensitive (HS+) and all others were identified as non-hormone sensitive (HS−). The monetary incentive delay (MID) task was administered during fMRI sessions at pre-treatment and during hormone withdrawal to assess brain activation during reward anticipation and feedback.
On average, anhedonia increased during addback and withdrawal in PPD+ but not PPD−. During reward feedback, both HS+ (n = 10) and HS− (n = 18) showed decreased activation in clusters in the right putamen (p < .031, FWE-corrected) and left postcentral and supramarginal gyri (p < .014, FWE-corrected) at the withdrawal scans, relative to pre-treatment scans.
A modest sample size, stringent exclusion criteria, and relative lack of diversity in study participants limit the generalizability of results.
Although results do not explain differential hormone sensitivity in depression, they demonstrate significant effects of reproductive hormones on reward-related brain function in women.
•Estradiol and progesterone administration triggered depression symptoms in women with a history of postpartum depression.•Estradiol and progesterone administration also decreased activity in brain areas that respond to rewards.•Changes in brain activity in the reward network caused by pregnancy hormones did not explain why some women experience postpartum depression while others do not.
The Health Resources and Services Administration (HRSA) began collecting data on intimate partner violence (IPV) and human trafficking (HT) in the 2020 Uniform Data System (UDS). We examined patients ...affected by IPV and HT served by HRSA-funded health centers in medically underserved US communities during the COVID-19 pandemic.
We established a baseline and measured trends in patient care by analyzing data from the 2020 (N = 28 590 897) and 2021 (N = 30 193 278) UDS. We conducted longitudinal ordinal logistic regression analyses to assess the association of care trends and organization-level and patient characteristics using proportional odds ratios (PORs) and 95% CIs.
The number of clinical visits for patients affected by IPV and HT decreased by 29.4% and 88.3%, respectively, from 2020 to 2021. Health centers serving a higher (vs lower) percentage of pediatric patients were more likely to continuously serve patients affected by IPV (POR = 2.58; 95% CI, 1.01-6.61) and HT (POR = 6.14; 95% CI, 2.06-18.29). Health centers serving (vs not serving) patients affected by IPV were associated with a higher percentage of patients who had limited English proficiency (POR = 1.77; 95% CI, 1.02-3.05) and Medicaid beneficiaries (POR = 2.88; 95% CI, 1.48-5.62), whereas health centers serving (vs not serving) patients affected by HT were associated with a higher percentage of female patients of reproductive age (POR = 15.89; 95% CI, 1.61-157.38) and urban settings (POR = 1.74; 95% CI, 1.26-2.37).
The number of clinical visits for patients affected by IPV and HT during the COVID-19 pandemic declined. Delayed care will pose challenges for future health care needs of these populations.
Previous studies have demonstrated the ability of the 11Craclopride positron emission tomography (PET) technique to measure behaviorally induced changes in endogenous dopamine transmission in humans. ...However, these studies have lacked well matched sensorimotor control conditions, making it difficult to know what sensory, cognitive, or motor features contributed to changes in dopaminergic activity. Here we report on 11Craclopride PET studies in which healthy humans performed card selection tasks for monetary rewards. During separate scans, subjects completed a variable ratio (VR) reward schedule with a 25% reward rate in which they did not know the outcome of their responses in advance, a fixed ratio (FR) 25% reward schedule in which outcomes were fully predictable, and a sensorimotor control (SC) condition involving similar sensory and motor demands but no rewards. Relative to the SC condition, the FR schedule produced only modest increases in dopamine transmission and no decreases relative to the SC condition. In contrast, the VR schedule produced significant increases in dopamine transmission in the left medial caudate nucleus while simultaneously producing significant decreases in other areas of the caudate and putamen. These data indicate: (1) the feasibility of measuring alterations in dopamine transmission even after controlling for sensorimotor features and (2) the complex and regionally specific influence of VR schedules on dopamine transmission. The implications of these results are discussed in relation to conflicting models of dopaminergic functioning arising from studies using electrophysiological and microdialysis techniques in animals.
Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD ...therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD.
In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes.
Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards.
The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.
•Brain inflammation has been observed in individuals with autism.•Brain inflammation impacts reward-related behaviors and dopamine functioning.•This review suggests that brain inflammation impairs ...reward processing in autism.•This linkage, suggests anti-inflammatory treatments should be investigated to treat autism.
Accumulating evidence suggests that autism spectrum disorder (ASD) may be conceptualized within a framework of reward processing impairments. The Social Motivation Theory of Autism posits that reduced motivation to interact with people and decreased pleasure derived from social interactions may derail typical social development and contribute to the emergence of core social communication deficits in ASD. Neuroinflammation may disrupt the development of mesolimbic dopaminergic systems that are critical for optimal functioning of social reward processing systems. This neuroinflammation-induced disturbance of mesolimbic dopaminergic functioning has been substantiated using maternal immune activation rodent models whose offspring show aberrant dopaminergic corticostriatal function, as well as behavioral characteristics of ASD model systems. Preclinical findings are in turn supported by clinical evidence of increased mesolimbic neuroinflammatory responses in individuals with ASD. This review summarizes evidence for reward processing deficits and neuroinflammatory impairments in ASD and examines how immune inflammatory dysregulation may impair the development of dopaminergic mesolimbic circuitry in ASD. Finally, future research directions examining neuroinflammatory effects on reward processing in ASD are proposed.
Fronto-limbic interactions facilitate the generation of task-relevant responses while inhibiting interference from emotionally distracting information. Schizophrenia is associated with deficits in ...both executive attention and affective regulation. This study aims to elucidate the neural correlates of emotion-attention regulation and shifting in schizophrenia.
We employed functional magnetic resonance imaging to probe the fronto-limbic regions in 16 adults with schizophrenia and 13 matched adults with no history of psychiatric illness. Subjects performed a forced-choice visual oddball task where they detected infrequent target circles embedded in a series of infrequent nontarget aversive and neutral pictures and frequent squares.
In control participants, target events activated a dorsal frontoparietal network, whereas these regions were deactivated by aversive stimuli. Conversely, ventral frontolimbic brain regions were activated by aversive stimuli and deactivated by target events. In the patient group, regional hemodynamic timecourses revealed not only reduced activation to target and aversive events in dorsal executive and ventral limbic regions, respectively, but also reduced deactivation to target and aversive stimuli in ventral and dorsal regions, respectively, relative to the control group. Patients further showed reduced spatial extent of activation in the right inferior frontal gyrus during the target and aversive conditions. Activation of the anterior cingulate to aversive images was inversely related to severity of avolition and anhedonia symptoms in the schizophrenia group.
These results suggest both frontal and limbic dysfunction in schizophrenia as well as aberrant reciprocal inhibitions between these regions during attention-emotion modulation in this disorder.
•Opiate users show less responsivity to substance-free activity reward anticipation.•Opiate users show greater responsivity to substance-free activity reward receipt.•Findings suggest challenges ...encoding stimuli-reward associations in opiate users.
Deficits in the ability to experience reward from natural, substance-free activities and stimuli is a common mechanism contributing to both opiate use disorder and depressive symptoms, and is a target of behavioral-focused treatments for substance use and depression. Although the neural response to monetary, positive affect-eliciting and social images has been investigated, the neural response to images representing substance-free activity engagement remains untested. The current study tested the neural response to anticipation and receipt of substance-free activity engagement images and monetary reward in opiate use disorder patients with elevated depressive symptoms compared to healthy controls.
Sixteen male opiate use disorder detoxification patients with elevated depressive symptoms (Beck Depression Inventory (BDI-II) ≥ 14) (OUDD Mage = 32.19 years, SD = 8.17 years) and seventeen male healthy controls (BDI-II < 14) (HC: Mage = 26.82 years, SD = 5.29 years) completed the Monetary Incentive Delay (MID) and newly developed Activity Incentive Delay (AID) tasks. Within- and between-group whole-brain contrasts tested activation during anticipation (reward-non-reward) and receipt (win-non-win) of substance-free activity image, monetary, and substance-free activity relative to monetary (AID-MID), reward.
OUDD demonstrated significantly lower activation in reward regions during anticipation and significantly greater activation during receipt of substance-free activity image reward compared to HC. OUDD demonstrated significantly lower activation during anticipation of substance-free activity reward relative to monetary reward, compared to HC.
The observed reduction in frontostriatal response to reward anticipation of substance-free activity engagement images in OUDD, yet increased neural response to reward receipt, supports theory linking reductions in reward processing with deficits in motivation for substance-free activity engagement.
We tested the prediction that resting frontal brain asymmetry would be a marker of vulnerability for depression among adolescents. Baseline electroencephalographic (EEG) activity was recorded from 12 ...to14-year-old adolescents whose mothers had a history of depression (high risk group) and whose mothers were lifetime-free of axis I psychopathology (low risk group). High risk adolescents demonstrated the hypothesized pattern of relative left frontal hypo-activity on alpha-band measures. Such effects were specific to the mid-frontal region and generally consistent across reference montages. Socio-economic status (SES) also predicted alpha asymmetry. When the effects of SES and risk status were jointly assessed, SES contributed unique variance to the prediction of frontal brain asymmetry. The implications of the observed relations among maternal depression, SES, and frontal brain asymmetry are discussed.
In two experimental sessions, we assessed early‐ and late‐onset acoustic startle eyeblink modulation and subjective ratings of emotional pictures by nondepressed participants and by unipolar ...depressed participants. Depressed participants were assessed before and after treatment with the antidepressant medication Bupropion SR. Both depressed and nondepressed participants exhibited arousal‐dependent startle modulation to early probes occurring 300 ms after picture onset. Nondepressed participants demonstrated the expected valence‐dependent startle modulation to late probes (3,500–4,500 ms post‐onset). In contrast, the late‐probe blink magnitudes of depressed patients were unrelated to picture valence. This pattern of group differences was not moderated by treatment. There were no between‐group differences in self‐report ratings to pictures. These results suggest that depression may be characterized by anomalous responses to affective stimuli and that startle modulation can be a more sensitive index of affective response deficits linked to depression than self‐report measures.
This study examined the effects of electroconvulsive therapy (ECT) treatment conditions, patient individual difference factors, and clinical outcome on global electroencephalogram (EEG) power during ...and immediately following ECT-induced seizures. Sixty-two patients were randomized to ECT conditions differing in electrode placement (right unilateral versus bilateral) and stimulus dosage (just above seizure threshold versus 2.5 times seizure threshold). At the second and penultimate treatments, global total power (1.5-28.5 Hz) and global power in specific frequency bands were quantified in 19-lead EEG recordings of the generalized seizure and the immediate postictal period. Seizures induced with high dosage, and to lesser extent, with bilateral electrode placement, resulted in greater global power. Patient age, initial seizure threshold, and baseline depression severity were inversely related to global power during seizures. While superior clinical outcome following ECT was associated with greater global power during seizures, this effect was small. The factors associated with more robust seizure expression also resulted in greater postictal bioelectric suppression. Associations with treatment parameters and patient variables were stronger at the second than penultimate treatment. We conclude that manipulations of ECT technique strongly determine the magnitude of seizure expression, but relations with clinical outcome are weak. The findings raise doubt about the clinical utility of algorithms based on analysis of EEG features to guide ECT parameter selection.
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